Chemical tailoring of self-associating poly(ethylene oxide)-block-poly(ester) copolymers for drug delivery applications

用于药物输送应用的自缔合聚（环氧乙烷）-嵌段-聚（酯）共聚物的化学定制

• 批准号: RGPIN-2014-03677
• 负责人: Lavasanifar, Afsaneh
• 金额: $ 1.82万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=610583
• 关键词: Chemical; tailoring; self; associating; poly

The main purpose of this research is to design and develop novel synthetic polymers that can adequately solubilize oily materials, and release them in an appropriate rate and location, but at the same time, are safe, degradable and environmentally friendly. Such compounds may find several applications in different natural science and engineering related fields. For instance, in agriculture, they may be used to deliver pesticides in a controlled manner. In oil industry, they may be used to clean water from oily waste and impurities. And in bio-medical field, they may be used to improve the function of current and emerging pharmaceuticals and/or diagnostic agents used in animals or human. In the previous phases of this NSERC funded project, we have developed and intellectually protected (with patent filings) a library of safe, degradable and environmentally friendly polymers and explored their application as novel pharmaceutical excipients for drug delivery applications. The copolymers within this library have been utilized to form core/shell structures in nanometer size range, namely polymeric micelles, that were able to encapsulate a number of drugs and drug-able genes as well as imaging probes, stabilize them in the harsh biological environment, reduce their exposure to healthy cells/tissues and at the same time direct the incorporated cargo towards target tissues and cells. This has enhanced the performance of incorporated cargo in treating or imaging of the disease (e.g., cancerous tissues). The aim of current proposal is to develop more advanced generations of these polymers and the associated nano-structures which can offer improved function in the solubilization and controlled delivery of diverse chemical structures. We propose to develop "intelligent" nano-materials based on innovative polymers that can keep their integrity and effectively solubilize small or large molecules of interest under normal physiological condition, but sense the presence of specific triggers (such as pH and/or enzymes), and dissociate in response to such triggers. Fulfillment of the objectives of this project will lead to the development of bio-materials that are more effective in solubilization of diverse drugs or imaging agents; and proficient in controlled delivery of incorporated cargo at appropriate rate and/or to the desired location. These materials will be designed to eventually dissociate and get eliminated from the body, not causing short- or long term harm to human or animals upon administration. Materials with such properties have a realistic prospect for use in pharmaceutical industry for the development of better drugs and/or diagnostic imaging tools. Moreover, these new materials can be developed further and optimized for application in other engineering fields as described above. Our specific goals in the current phase of this previously NSERC funded project are: 1. To prepare a new generation of biodegradable and bio-compatible polymers and their associated nano-structures; 2. characterize the efficacy of generated nano-materials for their stability, solubilization capacity and controlled delivery of model oily materials with diverse chemical structures in laboratory setting; and 3. characterize the fate of generated nano-materials and Incorporated cargo in animals.

这项研究的主要目的是设计和开发新型的合成聚合物，这些聚合物可以充分溶解油性材料，并以适当的速度和位置释放它们，但同时既安全，可降解又可以友好。这样的化合物可能在不同的自然科学和工程领域中找到了多个应用。例如，在农业中，它们可用于以受控方式运送农药。在石油工业中，它们可用于清洁油性废物和杂质中的水。在生物医学领域，它们可用于改善动物或人类使用的诊断药的当前和新兴药物的功能。 在这个由NSERC资助的项目的先前阶段中，我们已经开发了并受到智力保护（并附有专利申请），该库是安全，可降解和环保的聚合物的库，并探索了它们作为用于药物输送应用的新型药品赋形剂的应用。该库中的共聚物已被用来形成纳米尺寸范围内的核/外壳结构，即能够封装许多药物和可吸毒基因的聚合物胶束，以及成像探测，在苛刻的生物学环境中稳定它们，减少其对健康的细胞/组织/组织的暴露，并将其直接固定为量身网细胞，并朝着目标组织和细胞组成。这已经提高了综合货物在治疗或成像疾病（例如癌组织）中的性能。 当前建议的目的是开发这些聚合物的更先进的世代和相关的纳米结构，这些结构可以在溶解和控制的各种化学结构的溶解和受控递送方面提供改进的功能。我们建议基于创新的聚合物开发“智能”的纳米材料，这些纳米材料可以保持其完整性并有效地溶解在正常生理条件下的小或大分子，但要感知特定触发因素（例如pH和/或酶）的存在，并对此类触发器的响应进行解散。实现该项目的目标将导致生物材料的发展，这些物质在溶解多种药物或成像剂方面更有效；并以适当的速度和/或到所需的位置熟练熟练地交付合并的货物。这些材料的设计最终将解离并被脱离身体，不会在给药时对人或动物造成短期或长期伤害。具有此类特性的材料在制药行业中具有现实的前景，用于开发更好的药物和/或诊断成像工具。此外，这些新材料可以进一步开发，并在其他工程领域中进行优化，如上所述。 我们在此前由NSERC资助的项目的当前阶段中的具体目标是：1。准备新一代的可生物降解和生物兼容的聚合物及其相关的纳米结构； 2。表征产生的纳米材料的效果，以实现其稳定性，溶解能力和在实验室环境中具有多种化学结构的模型油性材料的控制递送；和3。是在动物中产生的纳米材料和掺入货物的命运。